Critical postnatal period for the induction of a long-term increase in the noradrenaline content of rat cerebellum by X-irradiation

Motor abnormalities and changes in the noradrenaline content and the cytoarchitecture of developing cerebellum following X-Irradiation at birth

“…In contrast, we have found a PN period (d 0-6) for the induction of both an increase in NA content and the abnormal disposition of Purkinje cells (see Fig. 1F-H) in adult CE, by neonatal X-irradiation (Dopico et al, 1991b), which might be interpreted again in the context of response of the NA afferents to X-irradiation-induced changes in the targets.…”

“…The increased NA content in dt rats is followed developmentally by a reduction in the sensitivity to the NAdepleting effect of reserpine (McKeon et al, 1986). In our model, we found no differences either in the effect of reserpine or the in vitro release of 3H-NA by Ro 4-1284, a reserpine-like agent (Dopico et al, 1991b). The elevated NA content with no impairment in the storage of the neurotransmitter might then result in an increased availability of NA for its targets.…”

“…Then, blocks were embedded in Paraplast after dehydration in a series of graded alcohol solutions, and cut on a Minot microtome. The sections obtained (10 µm) were stained with 0.1% toluidine Blue (aqueous solution) for 30 min, and mounted for light microscopy (Dopico et al, 1991b).…”

“…Animals were exposed to a single dose (5 Gy) of Xirradiation within the first 48 h after birth as described in Materials and Methods, and killed by decapitation at different times of postnatal (PN) life. Pictures show light micrographs of parasagittal sections (10-gm thick) through the cerebellar hemispheres stained with a modification of Nissl method (Dopico et al, 1991b). (a) At PN d 5, the cerebellar cortex of control rats shows the presence of numerous premitotic neuroblasts, which constitute the external granular layer (eg).…”

“…None of these abnormalities were found when the ionizing treatment was applied to adult rats, in which cerebellar connectivity had reached maturity (Dopico et al, 1989(Dopico et al, , 1990a. Furthermore, applying repeated low doses of X-rays in the early postnatal (PN) life, revealed a critical period for the induction of a permanent increase in the NA content of rat CE, as well as of the motor and histological abnormalities (Dopico et al, 1991b). These findings in adult rats raised the issue of whether the X-irradiation-induced increase in cerebellar NA content reflects a primary action of the ionizing noxa on NA afferents, which in turn could affect the development and final disposition of their main target cells in cerebellar cortex (i.e., Purkinje cells, Ito, 1984), or results as a consequence of a reactive response of the noradrenergic afferents to an effect of X-rays on target areas (in particular, Purkinje cells).…”